Pain is a subjective experience, influenced by physical, psychological, social, and spiritual factors. The concept of total pain acknowledges the importance of all these dimensions and that good pain relief is unlikely without attention to each aspect. Pain and diseases such as cancer are not synonymous: at least two thirds of patients experience pain at some time during the course of their illness, and most will need potent analgesics.
Synthetic opioids are a cornerstone of the management of cancer pain and postoperative pain and are used increasingly for the management of severe non-cancer pain. Understanding the metabolism of synthetic opioids is of great practical importance to primary care clinicians. Synthetic opioids metabolism is a vital safety consideration in older and medically complicated patients, who may be taking multiple medications and may have inflammation, impaired renal and hepatic function, and impaired immunity. Severe pain, such as lower back pain, also occurs in younger persons and is the leading cause of disability in younger than 45 years. In younger patients, physicians may be more concerned with synthetic opioids metabolism in reference to development of tolerance, impairment of skills and mental function, adverse events during pregnancy and lactation, and prevention of abuse by monitoring drug and metabolite levels.
Experienced clinicians are aware that the efficacy and tolerability of specific synthetic opioids may vary dramatically among patients and that trials of several synthetic opioids may be needed before finding one that provides an acceptable balance of analgesia and tolerability for an individual patient. Pharmacodynamic and pharmacokinetic differences underlie this variability of response. Pharmacodynamics refers to how a drug affects the body, whereas pharmacokinetics describes how the body alters the drug.
Pharmacokinetics contributes to the variability in response to synthetic opioids by affecting the bioavailability of a drug, the production of active or inactive metabolites, and their elimination from the body. Pharmacodynamic factors contributing to variability of response to synthetic opioids include between-patient differences in specific synthetic opioids receptors and between-synthetic opioids differences in binding to receptor subtypes. The receptor binding of synthetic opioids is imperfectly understood; hence, matching individual patients with specific synthetic opioids to optimize efficacy and tolerability remains a trial-and-error procedure.
Neurological disorders such as pain are a heterogeneous group of diseases of the nervous system, including the brain, spinal cord, and peripheral nerves that have much different aetiology. Many are hereditary; some are secondary to toxic or metabolic processes. Free radicals are highly reactive molecules or chemical species capable of independent existence. Generation of highly Reactive Oxygen Species (ROS) is an integral feature of normal cellular function like mitochondrial respiratory chain, phagocytosis and arachidonic acid metabolism. The release of oxygen free radicals has also been reported during the recovery phases from many pathological noxious stimuli to the cerebral tissues. Some of the pain associated neurological disorders include injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, post herpetic neuralgia, diabetic neuropathy, cancer pain, fibromyalgia and lower back pain.
Managing acute pathology of often relies on the addressing underlying pathology and symptoms of the disease. There is currently a need in the art for new compositions to treatment of severe pain.